BACKGROUND: Adults with severe mental illness (SMI) display an increased prevalence of HIV compared with the general population. Recommendations for provider-initiated testing in South Africa lack robust evidence because the studies - mainly from low-prevalence regions - overestimate the risk of HIV among adults with SMI. OBJECTIVE: We aimed to assess whether the mentally ill are a vulnerable population in South Africa. Methods. All new admissions to an acute psychiatric ward from July to December 2000 were tested for HIV anonymously and the results linked with socio-demographic and clinical data. We did a restricted analysis of black females from a population-based survey of black females with SMI. RESULTS: There were 216 admissions, of whom 206 were included in the analysis. The seroprevalence of HIV-1 was 29.1% (confidence interval 27.8 - 32.4); seroprevalence of HIV among the women was 40%. The following predicted HIV positivity: female (odds ratio (OR) 3.5 (1.7 - 6.9)), infections of the chest or central nervous system (OR 3.2 (1.4 - 7.5)), age group 30 - 39 years (OR 2.3 (1.1 - 4.8)) and aggression on admission. The age and sex ratios among the SMI group were similar to the general population. Adults with SMI have an almost three times greater prevalence of HIV than the general population, after controlling for age and gender. CONCLUSIONS: Adults with SMI are a vulnerable population; therefore, provider-initiated HIV testing and other prevention and treatment programmes must be tailored to their needs.